This research proposes to examine the binding of lipophilic polynuclear aromatic hydrocarbon carcinogens to serum lipoproteins (LP), correlating such binding to the component composition of the lipoproteins. Data show PAH carcinogens bound to LP enter cells potentiated level are subsequently to cellular DNA. We will investigate the LP mediated internalization of PAH carcinogens in vitro. Baboon smooth muscle cells, human lymphocytes, normal and LDL receptor deficient human fibroblast cell lines, and the rodent cell lines C3H/10T1/2 clone 8 and V-79 will be employed in this study. We propose to examine receptor mediated LP entry into cells as a route of PAH entry. We will assess LP stabilization of sequestered PAH carcinogens prior to and during cell entry of the LP from an aqueous environment. We will use V-79 to assess LP mediated PAH entry into cells and interaction with cellular DNA to produce detectable mutants and sister chromatid exchange. We will use differential transformation of 10T1/2 cells in the presence of PAH carcinogens and varying LP types and concentrations. We will use the smooth muscle cells (baboon embryonic) to assess LP mediated carcinogen transport into cells with subsequent metabolism of the carcinogens to reactive forms capable of binding cellular DNA. These studies will provide several levels of information related to the LP and LP-potentiated entry of carcinogen into cells. We will be able to examine the PAH entry, metabolism, binding to DNA, initiation of mutations, initiation of chromosomal defects, and initiation of transformation. We will also assess the initiation of DNA repair in these various cells exposed to different types and concentrations of LP. We will assess why human lipoproteins bind different levels of PAH carcinogens, and if the component composition of the lipoprotein dictates the PAH binding characteristics. This research crosses lines of disciplines between genetics, molecular biology, biochemistry, and clinical studies of atherogenesis and carcinogenesis. The interaction of LP with carcinogens in the production of human disease states dictates the scope of the research. We wish to understand how lipoproteins and lipophilic carcinogens interact in the currently known synergistic manner in the production of human disease.